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    • 专利摘要:
    METHOD OF MANUFACTURING A SYNTHETIC BONE PROSTHESIS AND SYNTHETIC BONE PROSTHESIS This is a resorbable tissue support structure manufactured from bioactive glass fiber that forms a rigid three-dimensional porous matrix that has a bioactive composition. A porosity in the form of an interconnected pore space is provided by the space between the bioactive glass fiber in the porous matrix. The strength of the bioresorbable matrix is provided by bioactive glass that fuses and binds the bioactive glass fiber into the rigid three-dimensional matrix. The resorbable tissue support structure supports tissue growth to provide osteoconductivity as a resorbable tissue support structure used for the repair of deteriorated and/or diseased bone tissue.
    公开号:BR112012000327B1
    申请号:R112012000327-5
    申请日:2010-07-08
    公开日:2021-04-20
    发明作者:James Jenq Liu；Juha-Pekka Nuutinen；Adam Wallen
    申请人:Bio2 Technologies, Inc；
    IPC主号:
    专利说明:

    FIELD OF THE INVENTION
    The present invention generally relates to the field of fibrous and porous medical implants. More specifically, the invention relates to a bioactive fibrous implant that has osteostimulating properties in in vivo media applications. FUNDAMENTALS OF THE INVENTION
    Prosthetic devices are often needed to repair defects in bone tissue in surgical and orthopedic procedures. Prostheses are increasingly needed to replace or repair diseased or deteriorated bone tissue in an elderly population and to improve the body's own mechanism to produce rapid healing of musculoskeletal injuries resulting from severe trauma or degenerative disease.
    Autograft and allograft procedures have been developed for the repair of bone defects. In autograft procedures, bone grafts are collected from a donor site in the patient, for example, from the iliac crest, to implant at the repair site to promote bone tissue regeneration. However, autograft procedures are particularly invasive, and pose a risk 25 of unnecessary infection and pain, and discomfort at the collection site. In allograft procedures, bone grafts . are used from a donor of the same species, but the use of these materials can increase the risk of infection, f disease transmission, and immune reactions, as well as religious objections. Consequently, synthetic materials and methods for implanting synthetic materials have been sought as an alternative to autograft and allograft.
    Synthetic prosthetic devices for repairing bone tissue defects have been developed in an attempt to provide a material with the mechanical properties of natural bone materials, while promoting bone tissue growth to provide a durable and permanent repair. A knowledge of the structure and biomechanical properties of bone, and an understanding of the bone healing process provide guidance on the desired properties and characteristics of an ideal synthetic prosthetic device for bone repair. These features include, but are not limited to: bio-resorbability so that the device effectively dissolves in the body without harmful side effects; osteostimulation and/or osteoconductivity to promote the growth of bone tissue in the device as the wound heals; and load bearing or weight distribution to support the repair site further exercises tissue as the wound heals to promote a durable repair.
    Materials developed to date have been successful in achieving at least some of the desired characteristics, but almost all materials compromise at least some aspect of the biomechanical needs of an ideal hard tissue support structure. BRIEF SUMMARY OF THE INVENTION
    The present invention achieves the objectives of a synthetic bone prosthesis 25 effective for the repair of bone defects by providing a material that is bio-resorbable, osteostimulating, and that. supports charge. The present invention provides a bio-resorbable (i.e., resorbable) tissue support structure of bioactive glass fiber with a bioactive glass bond in at least a portion of the fiber to form a rigid three-dimensional porous matrix. The porous matrix has an interconnected pore space with a pore size distribution in the range of approximately 10 µm to approximately 600 µm with porosity between 40% and 85% to provide osteoconductivity once implanted in the bone tissue. Embodiments of the present invention include space in the range of approximately 50 m and approximately 500 m.
    Methods of manufacturing a synthetic bone prosthesis in accordance with the present invention are also provided which include mixing bioactive fiber with a binder, a pore former, and a liquid to provide a plastically formable batch, and a formable batch knead for distribute the bioactive fiber into a substantially homogeneous mass of interwoven and overlapping bioactive fiber. The formable batch is dried, heated to remove a binder and pore former, and heated to a bond-forming temperature between the intertwined and overlapping bioactive glass fibers.
    These and other features of the present invention will become apparent from a reading of the following descriptions and can be accomplished by means of the instruments and combinations particularly pointed out in the appended claims. BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS
    The foregoing and other objects, features, and advantages of the invention will be apparent from the following detailed description of the various embodiments of the invention, as illustrated in the accompanying drawings in which the same reference characters refer to the same parts throughout. of the different views. The drawings are not necessarily to scale, instead the emphasis is (placed on illustrating the principles of the invention).
    FIGURE 1 is an optical micrograph at approximately 1000X magnification showing an embodiment of a bioactive tissue support structure in accordance with the present invention.
    FIGURE 2 is a flowchart of one embodiment of a method of the present invention for forming the bioactive tissue support structure of FIGURE 1.
    FIGURE 3 is a flowchart of an embodiment of a curing step in accordance with the method of the invention of FIGURE 2. FIGURE 4 is a schematic representation of an embodiment of an object manufactured in accordance with a method of the present invention.
    FIGURE 5 is a schematic representation of the object of FIGURE 4 after completion of a volatile component removal step of the method of the present invention.
    FIGURE 6 is a schematic representation of the object of FIGURE 5 after completion of a bond forming step of the method of the present invention.
    FIGURE 7 is a graph of a comparative analysis of various embodiments of resorbable tissue support structures of the present invention compared to known samples.
    FIGURE 8 is a side elevation view of a bioactive tissue support structure in accordance with the present invention produced in a spinal implant.
    FIGURE 9 is a side perspective view of a portion of a spine having the spinal implant of FIGURE 8 implanted in the intervertebral space.
    FIGURE 10 is a schematic drawing showing an isometric view of a bioactive tissue support structure in accordance with the present invention produced in a wedge osteotomy.
    FIGURE 11 is a schematic drawing showing an enlarged view of the wedge osteotomy of FIGURE 10 operable to be inserted into an osteotomy opening in a bone.
    While the drawings identified above set forth the presently described embodiments, other embodiments are also contemplated, as noted in the discussion. This description presents illustrative embodiments by way of representation and not limitation. Various other modifications and realizations can be devised by the 5 elements skilled in the art which fall within the scope and character of the principles of the realizations just described. DETAILED DESCRIPTION OF THE INVENTION
    The present invention provides a synthetic prosthetic tissue support structure for the repair of tissue defects. As used herein, the terms "synthetic prosthetic tissue supporting structure" and "bone tissue supporting structure" and "tissue supporting structure" and "synthetic bone prosthesis" in various forms may be used interchangeably throughout. In one embodiment, the synthetic prosthetic tissue support structure is bioresorbable once implanted into living tissue. In one embodiment, the synthetic prosthetic tissue support structure is osteoconductive once implanted into living tissue. In one embodiment, the synthetic prosthetic tissue support structure is osteostimulatory once implanted into living tissue. In one embodiment, the synthetic prosthetic tissue support structure supports load once implanted into living tissue.
    Several types of synthetic implants have been developed for tissue engineering applications in an attempt to provide a synthetic prosthetic device that simulates the properties of natural bone tissue and promotes tissue healing and repair. Metallic and biopersistent structures were developed to provide high strength in a pore structure that promotes the growth of new tissue. However, these materials are not bio-resorbable and must either be removed in subsequent surgical procedures or left inside the body for the lifetime of the patient. A disadvantage of biopersistent and biocompatible metallic implants is that the high load-bearing capacity does not transfer the regenerated tissue surrounding the implant. When hard tissue is formed, the tension load results in stronger tissue, but the metallic implant protects the newly formed bone from receiving this tension. The protection against bone tissue tension therefore results in weak bone tissue that can actually be reabsorbed by the body, which is an initiator of loosening of the prosthesis.
    Implants in living tissue elicit a biological response that depends on several factors, such as the composition of the implant. Biologically inactive materials are commonly encapsulated with fibrous tissue to isolate the implant from the host. Metals and most polymers produce this interfacial response, as in the case of near-inert ceramics such as alumina or zirconia. Biologically active materials or bioactive materials elicit a biolytic response that can produce an interfacial bond that holds the implant material to living tissue, as well as the interface that is formed when natural tissue is self-repairing. This interfacial bond can lead to an interface that stabilizes the support structure or implant in the bone bed and provides tension transfer from the support structure through the bonded interface within the bone tissue. When loads are applied to the repair, the bone tissue that includes the regenerated bone tissue is tensioned, thereby limiting the resorption of bone tissue due to stress protection. A bioresorbable material can elicit the same response as the bioactive material, but it can also exhibit complete chemical degradation by bodily fluid.
    The challenge of developing a resorbable tissue support structure using biologically active and resorbable materials is to obtain a load-bearing strength with sufficient porosity to promote bone tissue growth. Conventional bioactive bioglass and bioceramic materials in a porous form are not known to be inherently strong enough to provide load bearing strength like a synthetic prosthesis or implant. Conventional bioactive materials prepared in a tissue support structure with sufficient porosity to be osteostimulatory have not exhibited load-bearing strength. Similarly, conventional bioactive materials in a form that provide sufficient strength do not exhibit a pore structure that can be considered to be osteostimulating.
    Fiber-based structures are generally known to provide inherently greater strength to weight ratios, as the strength of an individual fiber can be significantly greater than powder-based or particulate-based materials of the same composition. A fiber can be produced with relatively few discontinuities that contribute to the formation of stress concentrations for fault propagation. In contrast, a powder-based or particulate-based material requires the formation of bonds between each of the adjacent particles, with each bonding interface potentially creating a stress concentration. In addition, the fiber-based structure provides stress relief and thus increased strength when the fiber-based structure is subjected to stress in which the failure of any one of the individual fibers does not propagate through the adjacent fibers. Consequently, a fiber-based structure exhibits superior mechanical strength properties in an equivalent size and porosity than a powder-based material of the same composition.
    Bioactive fiber-based materials have been proposed for tissue engineering applications, but these prior art materials compromise both the need for load-bearing and osteostimulating properties. For example, the teachings of Marcolongo et al. (U.S. Patent 5,645,934) describes a bioactive fiberglass composite structure braided with a thermoplastic polymer to provide load-bearing capacity but insufficient porosity to provide osteostimulation. Similarly, the teachings of Dunn et al. (US Patent 4,655,777) describe a bioactive glass fiber reinforced bioactive polymer matrix to provide a load-bearing hard tissue support structure, which is found in the dissolution of the bioactive polymer to facilitate bone tissue growth as required. surrounding bone heals. The teachings of Pirhonen (U.S. Patent 7,241,486) describe a porous bone filler material prepared by sintering bioactive glass fibers, but the resulting pore morphology is not well controlled to ensure osteoconductivity and/or osteostimulation when manufactured from a shape that has high strength for potentially load-bearing applications.
    The present invention provides a material for tissue engineering applications that is bio-resorbable, load-bearing, and osteostimulating with a pore structure that can be controlled and optimized to promote bone growth.
    FIGURE 1 is an optical micrograph at approximately 1000X magnification showing one embodiment of a bioactive tissue support structure 100 of the present invention. The bioactive tissue support structure 100 is a rigid three-dimensional matrix 110 that forms a structure that simulates bone structure in strength and in pore morphology. As used herein, the term "rigid" means that the structure has no significant yield on application of stress until it has fractured in the same way that natural bone would be considered to be a rigid structure. Support structure 100 is a porous material that has a network of pores 120 that are generally interconnected. In one embodiment, the interconnected pore network 120 provides osteoconductivity. As used herein, the term osteoconductive means that the material can facilitate the growth of bone tissue. The cancellous bone of a typical human has a compression crush strength ranging from approximately 4 to approximately 12 MPa with a modulus of elasticity ranging from approximately 0.1 to approximately 0.5 GPa.
    As will be shown below, the bioactive tissue support structure 100 of the present invention can provide a porous osteostimulating structure in a bioactive material with porosity greater than 50% and resistance to crushing by compression greater than 4 MPa up to and greater than 22 MPa .
    In one embodiment, the three-dimensional matrix 110 is formed of fibers that are bonded and fused into a rigid structure, with a composition that exhibits bioresorbability. The use of fibers as a raw material to create the three-dimensional matrix 110 provides a distinct advantage over the use of conventional bioactive powder or bio-resorbable raw materials. In one embodiment, the fiber-based raw material provides a structure that has more strength in a given porosity than a powder-based structure. In one embodiment, the use of fibers as the primary raw material results in a bioactive material that exhibits more uniform and controlled dissolution rates in body fluid.
    In one embodiment, the fiber-based material of the three-dimensional matrix 110 exhibits superior bio-resorbability characteristics over the same compositions in a powder-based or particle-based system. For example, dissolution rates are increasingly variable and thus unpredictable when the material exhibits grain boundaries, such as a form of powder-based material, or when the material is in a crystalline phase. Particle-based materials have been shown to exhibit rapid decrease in strength when dissolved by bodily fluids, and exhibit failures due to fatigue from crack propagation at particle grain boundaries. Since bioactive glass or fiber-shaped ceramic materials are generally amorphous, and the heat treatment processes of the methods of the present invention can better control the amount and degree of ordered structure and crystallinity, the supporting structure of fabric 100 of the present invention may exhibit more controlled dissolution rates with greater strength.
    The bioactive tissue support structure 100 of the present invention provides desired mechanical and chemical characteristics, combined with pore morphology to promote osteoconductivity. Pore network 120 is the natural interconnected porosity that results from space amidst the interwoven, non-woven fiber material in a structure that simulates the structure of natural bone. Furthermore, using the methods described here, pore size can be controlled and optimized to increase blood flow and body fluid within the supporting structure 100 and regenerated bone. For example, pore size and pore size distribution can be controlled by selecting pore formers and organic binders that are volatilized during the formation of support structure 100. Pore size and pore size distribution pore sizes can be determined by the particle size and particle size distribution of the pore former which includes a single mode pore size, a bimodal pore size distribution, and/or a multimodal pore size distribution. The porosity of the support structure 100 can range from approximately 40% to approximately 85%. In one embodiment, this band promotes the process of osteoinduction of regenerating tissue once implanted into living tissue while exhibiting load-bearing resistance.
    The support structure 100 is manufactured using fiber as a raw material. Fibers can be composed of a bioactive material that exhibits bio-resorbability. The term "fiber" as used herein is intended to describe a filament in a continuous or discontinuous form that has an aspect ratio greater than one, and formed from a fiber-forming process such as drawing, spinning, blowing, or other. similar process typically used in the formation of fibrous materials. Bioactive fibers can be manufactured from the bioactive composition that is capable of being formed into a fiber form, such as bioactive glasses, ceramics, and glass-ceramics. Fibers can be fabricated from bioactive composition precursors, which form a bioactive composition after formation of three-dimensional matrix 110 while forming support structure 100.
    Bioactive and bio-resorbable glass materials are generally known as a glass which has a composition of sodium carbonate, calcium carbonate, phosphorus pentoxide and silica, as a glass composition which has approximately 45-60 mol% silica and a 2-10 molar ratio of calcium to phosphate. Glass materials that have this or similar composition demonstrate the formation of a silica-rich layer and a calcium phosphate film on the surface of materials in an aqueous environment that readily binds the glass material to bone. Composition variations can be made by adding compositions such as magnesia, potassium oxide, boric oxide, and other compounds, although it is generally known that a silica content of between 45-60 mol% in the interfacial layer is advantageous for the formation of the silica-rich layer and a calcium phosphate film to promote the formation of bonds between the supporting structure and the natural bone material. For example, see the publication by Ogino, Ohuchi, and Bench, "Compositional Dependence of the Formation of Calcium Phosphate Films on Bioglass: J Biomed Mater Res. 1980, 14:55-64 (herein incorporated by reference).
    Glass composites are most easily formed into a fiber form when the material can be melted and drawn into a fiber in an amorphous form. Bioactive and bio-resorbable materials that can be manufactured into a fiber form without devitrification during the fiber making process require high silica content and both sodium oxide and potassium oxide to provide a mixed alkali effect to maintain an amorphous structure when formed into a fiber. Various mixed alkali compounds and high silica glasses that can be easily pulled onto the fibers have demonstrated both bioactivity and bioresorbability. For example, see the publication by Brink, Turunen, Happonen, and Yli-Urpo, "Compositional Dependence of Bioactivity of Glasses in the SyStCm Na2O-K2O-MgO-CaO-B2O3-P2O5-SiO2," J Biomed Mater Res. 1997; 37:114-121 (herein incorporated by reference), which describes at least ten different compositions in the Na20-K20-Mg0-Ca0-B2O3-P2O5-SiO2 system which can be readily drawn into fiber and which demonstrates bioactivity. In one embodiment, a bioactive and bioresorbable material that has a composition in respective molar amounts of 6% Na2O; 7.9% K2O; 7.7% MgO; 22.1% CaO; 0% B2O3; 1.7% P2O5; and 54.6% SiO2, (also referred to as 13-93 glass) provides bioactivity and bio-resorbability performance.
    Referring still to FIGURE 1, pore network 120 with three-dimensional matrix 110 has a unique structure 5 with properties that are particularly advantageous for bone tissue growth with a resorbable support structure 100. The characteristics of pore space 120 can be controlled through selection of volatile components, as described here below. The pore size distribution and the pore size are important features of the pore network 120, which can be specified and controlled, and thus, predetermined by selecting the volatile components that have specific particle sizes and distributions to provide a 15 structure that is osteoconductive while maintaining strength for load-bearing applications. Additionally, the pore network 120 exhibits better interconnectivity with relatively large nip sizes between the pores due to the position of the binder fibers and the pore former 20 over prior art materials which further increase the osteoconductivity of the resorbable tissue support structure 100 of the present invention. The pore network 120 arises from the space that results from the natural baling density of the fibrous materials, and the space that results from the displacement of fibers by the volatile components mixed with the fiber during formation of the resorbable support structure 100. As described further below, the bioactive material that forms the three-dimensional matrix 110 is manufactured by fusing and bonding the fibers 30 overlaid and interwoven with the glass. Fibers and glass and/or glass precursors are non-volatile components that are predisposed by forming a mixture with volatile components such as binders and pore formers, which include, for example, organic materials to predetermine pore size resulting, the pore distribution, and the size of the narrowing between the pores. Furthermore, the volatile components effectively increase the number of pore interconnects by increasing the size of the narrowing between the pores, which results in the pores being connected to multiple pores. Fiber volumes are de-agglomerated and distributed throughout the mixture, which results in a relative positioning of the fibrous materials in an overlapping and intertwined relationship within the volatile organic materials. After removal of the volatile components, and the fusion and bonding of the fiber and glass to form the three-dimensional matrix 110, the pore network 120 results from the space occupied by the volatile components.
    One objective of a resorbable support structure of the present invention is to facilitate the generation of tissue in situ as an implant in living tissue. Although there are several criteria for an ideal support structure for bone tissue repair, an important feature is a highly interconnected porous network with both pore sizes and pore interconnections large enough for cell migration, fluid exchange and eventually tissue growth and vascularization (eg penetration of blood vessels). The resorbable tissue support structure 100 of the present invention is a porous structure with pore size and pore interconnectivity that is particularly adapted for bone tissue growth. The pore network 120 has a pore size that can be controlled through the selection of volatile components used to fabricate the resorbable tissue support structure 100, to provide an average pore size of at least 100 µm. Embodiments of the resorbable tissue support structure 100 have an average pore size in the range of approximately 10 µm to approximately 600 µm, and alternatively, an average pore size in the range of approximately 100 µm to approximately 500 µm. The volatile components, which include the organic binder and the pore formers, which form the pores, ensure a high degree of interconnectivity with large pore narrowing sizes in the three-dimensional matrix. It may be desirable to have a pore size distribution that is smaller than the pore size that can be determined by in vitro analysis, wherein the pore size will grow as the three-dimensional matrix 120 is dissolved and resorbed in the body. In this way, the load-bearing capabilities of this material are increased with the initial implant, with regenerated bone tissue bearing more of the load as it regenerates while the resorbable tissue support structure 100 dissolves in the body.
    Referring to FIGURE 2, an embodiment of a method 200 of forming the bioactive tissue support structure 100 is shown. In general, fiber volume 210 is mixed with a binder 230 and a liquid 250 to form a plastically moldable material. , which is then cured to form the bioactive tissue support structure 100. Curing step 280 selectively removes volatile elements from the mixture, leaving pore space 120 open and 25 interconnected, and effectively fuses and bonds the fibers 210 to the matrix three-dimensional rigid 110.
    Fiber bulk 210 can be provided in bulk, or as chopped fibers. The diameter of fiber 210 can range from approximately 1 to approximately 200 µm and typically 30 between approximately 5 and approximately 100 µm. Fibers 210 of this type are typically produced with a relatively narrow and controlled distribution of fiber diameters, and fibers of a given diameter may be used, or a mixture of fibers having a range of fiber diameters may be used. The diameter of the fibers 210 will influence the pore size distribution and pore size resulting from the porous structure, as well as the size and thickness of the three-dimensional matrix 110, which will influence not only the osteoconductivity of the supporting structure 100, but also the rate at which the support structure 100 is dissolved by bodily fluids when implanted into living tissue and the resulting strength characteristics, which include compressive strength and modulus of elasticity.
    Binder 230 and liquid 250, when mixed with fiber 210, create a plastically formable batch blend that allows fibers 210 to be evenly distributed throughout the batch, while providing green resistance to allow the batch material to be formed. in a desired manner in the subsequent forming step 270. Since the organic binder material can be used as binder 230, such as methylcellulose, hydroxypropyl methylcellulose (HPMC), ethylcellulose, and combinations thereof. Binder 230 can include materials such as polyethylene, polypropylene, polybutene, polystyrene, polyvinyl acetate, polyester, isotactic polypropylene, atactic polypropylene, polysulfone, polyacetal polymers, polymethyl methacrylate, fumaron-indan copolymer, ethylene vinyl acetate copolymer, copolymer of styrene-butadiene, acrylic rubber, polyvinyl butyral, ionomeric resin, epoxy resin, nylon, phenol formaldehyde, furfural phenol, paraffin wax, wax emulsions, microcrystalline wax, celluloses, dextrins, chlorinated hydrocarbons, refined alginates, starches, gelatins , lignins, rubbers, acrylics, bitumen, casein, gums, albumins, proteins, glycols, hydroxyethyl cellulose, sodium carbomethylcellulose, polyvinyl alcohol, polyvinyl pyrrolidone, polyethylene oxide, polyacrylamides, polyethyleneimine, agar, agarose, molasses, dextrins, starch, lignosulfonates , licolignin liquor, sodium alginate, 5 gum arabic, xanthan gum, tragacanth to, karaya gum, locust bean gum, Irish moss, scleroglucan, acrylics, and cationic galatomannan, or combinations thereof. Although various binders 230 are listed above, it will be appreciated that other binders may be used. Binder 230 provides the desired rheology of the plastic batch material in order to form a desired object and maintain the relative position of fibers 210 in the mixture while the object is formed, while remaining inert with respect to the bioactive materials. The physical properties of the binder 230 will influence the pore size distribution and the pore size of the pore space 120 for the support structure 100. Preferably, the binder 230 is capable of thermal disintegration, or selective dissolution, without impact the chemical composition of the bioactive components, which include fiber 210.
    Fluid 250 is added as needed to achieve a desired rheology in the appropriate plastic batch material to form the plastic batch material into the desired object in the subsequent forming step 270. Water is typically used, although solvents of various types can be used. Rheological measurements can be made during blending step 260 to assess the plasticity and cohesive strength of the blend prior to forming step 270.
    Pore formers 240 may be included in the blend to increase the pore space 120 of the bioactive support structure 100. Pore formers are non-reactive materials that take up volume in the plastic batch material during blending step 260 and the step of formation 270. When used, the particle size and size distribution of the pore former 240 will influence the pore size distribution and the resulting pore size of the pore space 120 of the support structure 100. The particle sizes may typically range from approximately 25 µm or less to approximately 450 µm or more, or alternatively, the particle size for the pore former may be a function of fiber diameter 10 210 ranging from approximately 0.1 to approximately 100 times the fiber diameter 210. Pore former 240 should be readily removable during curing step 280 without significantly disrupting the relative position of the surrounding fibers. 210. In one embodiment of the invention, the pore former 240 may be removed through pyrolysis or thermal degradation, or volatilization at elevated temperatures during the curing step 280. For example, microwax emulsions, phenolic resin particles, flour, starch, or carbon particles may be included in the mixture as the pore former 240. Other pore formers 240 may include carbon black, activated carbon, graphite flakes, synthetic graphite, wood flour, modified starch, celluloses , coconut shells, latex spheres, poultry seeds, sawdust, pyrolyzable polymers, poly(25-alkyl methacrylate), polymethyl methacrylate, polyethyl methacrylate, polyn-butyl methacrylate, polyethers, polytetrahydrofuran, poly(1,3- dioxolane), poly(alkalene oxides), polyethylene oxide, polypropylene oxide, methacrylate copolymers, polyisobutylene, polytrimethylene carbonate, polyethylene oxalate, polybeta-propiolactone, polyd. elta-valerolactone, polyethylene carbonate, polypropylene carbonate, vinyl toluene/alpha-methylstyrene copolymer, styrene/alpha-methylstyrene copolymers, and sulfur dioxide-olefin copolymers. Pore formers 240 can generally be defined as organic or inorganic, with organic typically burning at a lower temperature than inorganic. 5 Although various pore formers 240 are listed above, it will be appreciated that other pore formers 240 can be used. Pore formers 240 can be, though need not be, completely biocompatible as they are removed from the support structure 100 during processing.
    A binding agent 220 may be included in the mixture to promote strength and performance of the resulting bioactive support structure 100. The binding agent 220 may include powder-based material of the same composition as the fiber volume 210, or it may include powder-based material of a different composition. As will be explained further in detail below, additives based on bonding agent 220 increase the binding strength of the intertwined fibers 210 that form the three-dimensional matrix 110 20 by forming bonds between adjacent and cross-linked fibers 210. The bonding agent 220 can be bioactive glass, ceramic glass, ceramic, or precursors thereof.
    The relative amounts of the respective materials, which include fiber volume 210, binder 230, and liquid 250 depend on the total porosity desired in the bioactive tissue support structure 100. For example, to provide a support structure 100 that has approximately 60% porosity, non-volatile components 275, such as fiber 210, should equal approximately 40% of the mixture by volume. The relative amount of volatile components 285, such as binder 230 and liquid 250 would equal approximately 60% of the mixture by volume, with the relative amount of binder to liquid determined by the desired rheology of the mixture. In addition, to produce a support structure 100 that has increased porosity by pore former 240, the amount of volatile components 285 is adjusted to include volatile pore former 240. Similarly, to produce a support structure 100 which has increased strength by binding agent 220, the amount of non-volatile components 275 would be adjusted to include non-volatile binding agent 220. It can be appreciated that the relative amounts of non-volatile components 275 and volatile components 285 and the resulting porosity of Support structure 100 will vary as material density may vary due to the reaction of the 15 components during curing step 280. Specific examples are provided below.
    In the mixing step 260, fiber 210, binder 230, liquid 250, pore former 240 and/or bonding agent 220, if included, are mixed into a homogeneous mass 20 of a uniform plastically deformable mixture.
    Mixing step 260 may include dry mixing, wet mixing, shear mixing, and kneading, which may be necessary to evenly distribute the material into a homogeneous mass while imparting the necessary shear forces to break and distribute or deagglomerate the fibers 210 with the non-fibrous materials. The amount of mixing, shearing, and kneading, and the duration of these mixing processes depend on the selection of fibers 210 and non-fibrous materials, along with the selection of the type of mixing equipment used during the mixing step 260, in order to obtain a uniform and consistent distribution of the materials within the mixture, with the desired rheological properties to form the object in the subsequent forming step 270. The mixture can be carried out using industrial mixing equipment such as batch mixers, mixers shears, and/or kneaders.
    Forming step 270 forms the blending of blending step 260 into the object that will become bioactive tissue support structure 100. Forming step 270 can include extrusion, lamination, pressure melting, or molding into virtually any shape. desired in order to provide a coarsely formed object that can be cured in the curing step 280 to provide the support structure 100. It will be appreciated that the final dimensions of the support structure 100 may be different from the object formed in the forming step 270 , due to shrinkage of the object during curing step 280, and additionally machine making and final shaping may be necessary to meet the specified dimensional requirements. In an exemplary embodiment to provide samples for mechanical and in vitro and in vivo testing, forming step 270 forces the mixture into a cylindrical rod using an extruder plunger which forces the mixture through a round mold.
    The object is then cured on the bioactive tissue support structure 100 in the healing step 280, as further described with reference to FIGURE 3. In the embodiment shown in FIGURE 3, the healing step 280 can be performed as a three-phase sequence. : a drying step 310; a volatile component removal step 320; and a bond-forming step 330. In the first stage, drying 310, the formed object is dried by removing the liquid using slightly elevated temperature heat with or without extruded convection to gradually remove the liquid. Various methods of heating the object can be used which include, but are not limited to, heated air convection heating, vacuum freeze drying, solvent extraction, microwave drying methods or electromagnetic/radio frequency (RF). The liquid within the formed object is preferably removed not too quickly to avoid drying cracks due to shrinkage. Typically, for water-based systems, the formed object can be dried when exposed to temperatures between approximately 90 °C and approximately 150°C for a period of approximately 10 hours, although the actual drying time may vary due to size and object shape, with larger, more massive objects taking longer to dry. In the case of microwave or RF energy drying, the liquid itself, and/or other components of the object, adsorb the radiated energy to generate heat more evenly throughout the material. During drying step 310, depending on the selection of materials used as volatile components, binder 230 may freeze or gel to provide greater green resistance to provide rigidity and strength in the object for subsequent handling.
    Once the object is dry, or substantially free of component liquid 250 by drying step 310, the next step of curing step 280 proceeds to volatile component removal step 320. This step removes the 25 volatile components (by example, the binder 230 and the pore former 240) of the object leaving only the non-volatile components that form the three-dimensional matrix 110 of the tissue support structure 100. The volatile components can be removed, for example, by pyrolysis or by thermal degradation, or solvent extraction. The volatile component removal step 320 can be further analyzed in a sequence of component removal steps, such as a binder burning step 340 followed by a pore-former removal step 350, when volatile components 285 are selected from so that the volatile component removal step 320 can sequentially remove the components. For example, HPMC used as a 230 binder will thermally decompose at approximately 300°C. A 220 graphite pore former will oxidize to carbon dioxide when heated to approximately 600 °C in the presence of oxygen. Similarly, flour or starch, when used as a 220 pore former, will thermally decompose at temperatures between approximately 300 °C and approximately 600 °C. Consequently, the formed object composed of a binder 230 of HPMC and a pore former 220 of graphite particles, can be processed in the volatile component removal step 320 by subjecting the object to a two-step scheme for removing the binder 230 and then pore former 220. In this example, the binder firing step 340 can be carried out at a temperature of at least approximately 300°C, but less than approximately 600°C for a period of time. The pore former 350 removal step can then be performed by increasing the temperature to at least approximately 600°C with the inclusion of oxygen in the heating chamber. This thermally sequenced volatile component 25 removal step 320 provides for a controlled removal of the volatile components 285 while maintaining the relative position of the non-volatile components 275 in the formed object.
    FIGURE 4 depicts a schematic representation of various components of the object formed prior to the volatile component removal step 320. Fibers 210 are interwoven with a mixture of binder 230 and pore former 240. Optionally, binding agent 220 can be further distributed in the mix (not shown for clarity). FIGURE 5 depicts a schematic representation of the object formed after completion of the volatile component removal step 320. The fibers 210 maintain their relative position as determined from the mixture of the 5 fibers 210 with the volatile components 285 as the volatile components 285 are removed . After completion of the removal of volatile components 285, the mechanical strength of the object may be quite fragile, and handling of the object in this state must be performed with care. In one embodiment, each phase of the curing step 280 is performed in the same oven or oven. In one embodiment, a handling tray is provided, on which the object can be processed to minimize damage caused by handling.
    FIGURE 6 depicts a schematic representation of the object formed after completion of the last step of curing step 280, bond formation 330. Pore space 120 is created where binder 230 and pore former 240 have been removed , and the fibers 210 are fused and bonded in the three-dimensional matrix 110. The characteristics of the volatile components 285, which include the size of the pore former 240 and/or the particle size distribution of the pore former 240 and/or the The relative amount of binder 230 together cooperate to predetermine the resulting pore size, pore size distribution, and pore interconnectivity of the resulting tissue support structure 100. The bonding agent 220 and the glass bonds that they form in overlapping nodes 610 and adjacent nodes 620 of the three-dimensional array 110 provide structural integrity of the resulting three-dimensional array 110.
    To demonstrate the effect of combining the features of the present invention, a comparative analysis 700 is shown in FIGURE 7. Five comparative samples (710, 720, 730, 740, and 750) were prepared and analyzed for compressive strength (in Mpa) and porosity (as a percentage). Sample 710 demonstrates the strength/porosity relationship for a porous structure based on bioactive glass powder 13-93. Sample 710 was prepared from a mixture of 5 grams of 13-93 bioactive glass powder, with 2 grams of HPMC organic binder, and water to provide a batch of plastic, extruded as a 14 mm diameter stick, and sintered into a porous form at a plurality of sintering temperatures. Sample 720 10 was prepared from a mixture of 13-93 bioactive fiberglass with 2 grams of HPMC organic binder, and water to provide a plastic batch, extruded as a 14 mm diameter stick, and cured in a it forms porous at a plurality of bond forming temperatures, as described above with respect to FIGURE 3. Both sample 710 and sample 720 do not include a pore former 240. As described above, the strength/porosity ratio for the system The fiber-based sample of sample 720 is improved over the powder-based sample 710. In sample 720, the organic binder, as a volatile component 285, positions the fiber with the space between the fibers predetermined by the volatile component 285 (here , the organic binder 230) to increase the porosity on the powder-based sample of the same effective strength.
    To demonstrate the effect of adding a 240 pore former, sample 730 was prepared from a mixture of bioactive glass powder 13-93 with 2 grams of HPMC organic binder and 1.5 grams of PMMA of one size of the 100 µm particle as a pore former 240 and water 30 to provide a batch of plastic, extruded as a rod 14 mm in diameter, and cured into a porous form at a plurality of sintering temperatures. Sample 740 was prepared from a mixture of 5 grams of 13-93 bioactive glass fiber with 2 grams of HPMC organic binder and 1.5 grams of PMMA with a particle size of 100 µm as a pore former 240 and water to provide a batch of plastic, extruded as a rod 14 mm in diameter, and cured into a porous shape at a plurality of bond forming temperatures. Sample 750 was prepared from a mixture of 5 grams of 13-93 bioactive glass fiber with 2 grams of HPMC organic binder and 7 grams of 4015 graphite powder which has a particle size distribution of between approximately 150 to approximately 425 µm as a pore former 240, but with addition of various amounts of bioactive glass powder 13-93 as a bonding agent 220, which was cured at a bond-forming temperature of approximately 800°C. Again, comparative fiber-based samples 740 and 750 exhibit a strength/porosity ratio that exceeds the performance of samples 710 and 730. Pore former 240 and binder 230 cooperate to predetermine the resulting pore size, distribution of pore size, and sample pore interconnectivity, with greater strength for a given porosity over conventional methods and devices.
    Referring to FIGURE 3, bond-forming step 330 converts the non-volatile components 275, which include the fiber volume 210, into the rigid three-dimensional matrix 110 of the bioactive tissue support structure 100 while maintaining the pore space 120 created by the removing volatile components 275. Bond-forming step 330 heats non-volatile components 275 to a temperature at which volume of fibers 210 bonds to adjacent and overlapping fibers 210, and for a duration sufficient to form bonds, without melting the fibers 210, and thereby destroying the relative positioning of the non-volatile components 275. The bond-forming temperature and duration depends on the chemical composition of the non-volatile components 275, which includes the volume of fibers 210. Bioactive glass fiber or powder of a particular composition exhibits softening and a plastic deformability without fracture at a glass transition temperature. Glass materials typically have a devitrification temperature at which the amorphous glass structure crystallizes. In one embodiment of the invention, the bond forming temperature in bond forming step 330 is in the operating range between the glass transition temperature and the devitrification temperature. For example, the bond forming temperature for bioactive glass composition 13-93 can be above the glass transition temperature of approximately 606°C and be less than the devitrification temperature of approximately 851°C.
    In bond forming step 330, the formed object is heated to the bond forming temperature which results in the formation of glass bonds in overlapping nodes 610 and adjacent nodes 620 of the fiber structure. The bonds are formed in overlapping nodes 610 and adjacent nodes 620 of the fiber structure through a reaction of the binding agent 220 which flows around the fibers 210, reacting with the fibers 210 to form a coating of glass and/or bonds of glass. In the bond-forming step 330, the material of the fibers 210 can participate in the chemical reaction with the bonding agent 220, or the fibers 210 can remain inert with respect to a reaction of the bonding agent 220. Additionally, the volume of fibers 210 can be a mixture of fiber compositions, with a part or all of the fibers 210 participating in a reaction that forms bonds to create the three-dimensional matrix 110.
    The duration of bonding step 330 depends on the temperature profile during bonding step 330, wherein the time at temperature of bonding the fibers 210 is limited to a relatively short duration so that the position relative of non-volatile components 275, which includes fiber volume 210, does not change significantly. The pore size, the pore size distribution, and the interconnectivity between the pores in the formed object are determined by the relative position of the fiber volume 210 by the volatile components 285. While 10 the volatile components 285 are likely burned from the formed object by time where bond formation temperature is reached, the relative positioning of fibers 210 and non-volatile components 275 do not change significantly. The formed object will likely undergo slight or lesser densification during bonding step 330, but control of pore size and pore size distribution can be maintained, and therefore predetermined by selecting a particle size for the pore former 240 which is slightly oversize or 20 adjust the relative amount of volatile components 285 to account for the expected densification.
    In one embodiment of the invention, binding agent 220 is a bioactive glass material based on fine powder or nanoparticle sizes (eg, 1 to 100 nanometers). 25 In this embodiment, the small particle sizes react more quickly at or near the glass transition temperature of the material composition, and form a glass that covers and bonds the overlapping nodes 610 and adjacent nodes 620 of the fiber structure before the Fiber material will be noticeably affected by exposure to temperature at or near its glass transition temperature. In this embodiment, for the binding agent 220 to be more reactive than the volume of fibers 210, the particle size can be in the range of 1 to 1,000 times smaller than the diameter of the fibers 210, for example, in the range of 10 microns to 10 nanometers when using 10 microns diameter fiber volume 210. Nanoparticle size powder can be produced by grinding bioactive glass material in a grinding or comminution process such as impact grinding or friction grinding into a ball mill or media mill.
    The temperature profile of bond-forming step 330 can be controlled to control the amount of crystallization and/or minimize devitrification of the resulting three-dimensional matrix 110. As described above, bioactive glass and bioresorbable glass compounds exhibit more dissolution rates controlled and predictable in living tissue when the amount of accessible grain boundaries of the 15 materials is minimized. These bioactive and bioresorbable materials exhibit superior performance as a bioactive device due to the amorphous structure of the material when fabricated from fibers 210, and the controlled degree of crystallinity that occurs during heat treatment processing during the bond forming step 330 Therefore, in one embodiment of the method of the present invention, the temperature profile of the bond forming step 330 is adapted to bond the fiber structure without increasing the grain boundaries in the non-volatile materials 275.
    In one embodiment of the method of the present invention, the bond-forming temperature exceeds the fiber volume devitrification temperature 210 during bond-forming step 330. Bioactive glass compositions may exhibit a narrow operating range between their temperature of glass transition and crystallization temperature. In this embodiment, crystallization of fibers 210 may not be avoided in order to promote the formation of bonds between overlapping and adjacent nodes of fibers 210 in the structure. For example, bioactive glass in composition 45S5 has an initial glass transition temperature of approximately 550°C and a devitrification temperature of approximately 580°C with multi-phase crystallization temperatures at temperatures of approximately 610, approximately 800, and approximately 850°C. With such a narrow operating range, forming a glass bond using the same composition as a bonding agent 220 is difficult to accomplish, and as such, the bond forming temperature may require bond forming temperatures at excess of approximately 900°C to form the glass bonds. In an alternative embodiment, the bond-forming temperature may exceed the crystallization temperature of the fibers 210, yet still fall within the working range of the composition of a bioactive glass in a powder form as a bonding agent 220. In this embodiment, the glass fibers 210 of a first composition may crystallize, with glass bonds of a second composition forming at the overlapping and adjacent nodes of the fiber structure. For example, a composition of 13-93 in the form of a powder as a bonding agent 220 can be used with bioactive glass fibers in a 45S5 composition, to form a glass bond above the glass transition temperature of the composition. 13-93, but less than the composition devitrification temperature of 13-93, but exceeds the glass fiber composition devitrification temperature 45S5 to form a formed composite object.
    In one embodiment of the invention, the temperature profile of bond-forming step 330 is configured to reach a bond-forming temperature quickly and briefly, with rapid cooling to prevent devitrification of the resulting bioactive material. Various heating methods can be used to provide this heating profile, such as forced convection like a greenhouse, which heats the object directly in a flame, laser, or other focused heating methods. In this embodiment, the focused heating method is a secondary heating method that complements a primary heating method, such as a stove or oven heating apparatus. The secondary heating method provides brief thermal shift to the bond forming temperature, with rapid recovery to a temperature lower than the glass transition temperature to avoid devitrification of the resulting three-dimensional matrix 110.
    In one embodiment of the invention, combustion of pore former 240 can be used to provide rapid and uniform heating throughout the object as a secondary heating method during bond forming step 330. In that embodiment, pore former 240 is a combustible material, such as carbon or graphite, or polymers, such as polymethyl methacrylate, which exothermically oxidize at elevated temperatures. Curing step 280 must initially heat in an inert or stagnant air oven or in an environment to burn any binder materials 230. The pore former 340 removal step is controlled by the environment by purging with an inert gas such as nitrogen, until which temperature is greater than the combustion temperature of the pore former, and nearly that of the desired bond forming temperature. Oxygen is introduced at high temperature, so that when the pore-former oxidizes, the temperature of the non-volatile materials can be locally raised at or above the glass transition temperature, or the bond-forming temperature, until the former. pores is completely burned. At that point, the temperature can be reduced to avoid devitrification and/or the growth of grain boundaries in and into the resulting structure.
    In yet another embodiment of the invention, the curing step 280 can be performed using a primary heat source, such as an oven or oven, with a secondary heat source that completes the oven or oven to heat quickly and evenly the object at the desired temperature for the bond-forming step to control the degree of crystallinity that should occur as a function of time and temperature. In this embodiment, a flame heat source can be applied directly to the object while it is in the stove or oven.
    The bonds formed between overlapping and adjacent knots of the intertwined fibers that form the three-dimensional matrix 110 can be glass bonds that have a composition substantially the same as the composition of the bulk fibers 210. The bonds can also be the result of a reaction between the bulk of fibers 210 and bonding agent 220 to form a glass bond that has a composition that is substantially different from the composition of fiber volume 210. Due to regulatory needs regarding approval of materials for use as a medical device or implant, it may be desirable to use compositions of materials approved as raw materials that are not significantly altered by the device manufacturing methods and processes. Alternatively, it may be desirable to use raw materials that are precursors to an approved material composition that forms the desired composition during device fabrication methods and processes. The present invention provides a bioactive, resorbable tissue support structure device that can be fabricated using a variety of clinically approved materials, or fabricated from a clinically approved composition of materials.
    The resorbable tissue support structures of the present invention can be used in procedures such as an osteotomy (e.g., in the hip, knee, hand, and jaw), a repair of a structural flaw in a spinal column (e.g., an intervertebral prosthesis , laminar prosthesis, sacral bone prosthesis, vertebral body prosthesis and facet prosthesis), a bone defect filling, fracture revision surgery, tumor resection surgery, hip and knee prostheses, bone augmentation, 10 tooth extractions, arthrodesis long bones, ankle and foot arthrodesis, which includes subtalar implants, and screw fixation pins. The resorbable tissue support structures of the present invention can be used in long bones, which include, but are not limited to, ribs, clavicle, femur, tibia, and fibula of the leg, humerus, radius, and ulna of the arm, metacarpals. and metatarsals of the hands and feet, and phalanges of the fingers and toes. The resorbable tissue support structures of the present invention can be used in short bones, which include, but are not limited to, the carpus and tarsi, the patella, along with other sesamoid bones. The resorbable tissue support structures of the present invention can be used in other bones, including, but not limited to, the skull, jaw, sternum, vertebrae, and sacrum. In one embodiment, the tissue support structure of the present invention has high load-bearing capabilities compared to conventional devices. In one embodiment, the tissue support structure of the present invention requires less material to be implanted compared to conventional devices.
    In addition, the use of the fabric support structure of the present invention requires less auxiliary fixation due to the strength of the material. In this way, surgical procedures for device implantation are less invasive, more easily performed, and do not require subsequent surgical procedures to remove instruments and auxiliary fixtures.
    In a specific application, a tissue support structure of the present invention, fabricated as described above, may be used as a spinal implant 800 as depicted in FIGURE 8 and FIGURE 9. Referring to FIGURE 8 and FIGURE 9, spinal implant 800 includes a body 810 having a wall 820 sized to fit into a space S between the adjacent vertebra V to maintain the space S. Device 800 is formed from bioactive glass fibers that can be formed into the desired shape. with the use of extrusion methods to form a cylindrical shape that can be cut or machined to a desired size. Wall 820 has a height h that corresponds to height H of space S. In one embodiment, height h of wall 820 is slightly greater than height H of intervertebral space S. Wall 820 is adjacent to and between an upper engaging surface 840 and a lower engagement surface 850 that are configured to engage the adjacent vertebra V as shown in FIGURE 9.
    In another specific application, a tissue support structure of the present invention, fabricated as described above, may be used as a 1000 wedge osteotomy implant as depicted in FIGURES 10 and 11. Referring to FIGURE 10 and FIGURE 11 , the osteotomy implant 1000 can generally be described as a wedge designed to conform to an anatomical cross section of, for example, a tibia, thereby providing mechanical support for a substantial portion of a surface of the tibia. The osteotomy implant is formed from the bonded bioactive glass fibers and fused into a porous material that can be formed from an extruded rectangular block, and cut or machined contoured into a wedge shape to the desired size. The proximal 1010 aspect of the 1000 implant is characterized by a curvilinear contour. The distal aspect 1020 conforms to the shape of a tibial bone in its implanted location. The thickness of the 1000 implant can range from approximately five millimeters to approximately twenty millimeters depending on the patient's size and degree of deformity. The degree of angulation between the upper and lower surfaces of the wedge can also be varied.
    FIGURE 11 illustrates a method for using the 1000 wedge osteotomy implant to realign an abnormally angled knee. A transverse incision is made in a midline aspect of the tibia while leaving a lateral portion of the tibia intact and aligning the upper 1050 and lower 1040 tibia at a predetermined angle to create a gap 1030. The implant is substantially wedge-shaped 1000 is inserted into space 1030 to stabilize the tibia parts as it heals into the desired position with implant 1000 dissolving into the body as described here. Fixation pins can be applied as needed to stabilize the tibia as the bone regenerates and heals the implant site.
    In general, the use of a resorbable bone tissue support structure of the present invention as a bone graft involves surgical procedures that are similar to the use of autologous bone grafts or allografts. Bone grafting can often be performed as a single procedure if enough material is used to fill and stabilize the implant site. In one embodiment, fixation pins can be inserted into the surrounding natural bone, and/or into and through the resorbable bone tissue support structure. The resorbable bone tissue support structure is inserted into one location and secured in position. The area is then closed and after a certain period of healing and maturation, the bone will regenerate and become solidly fused.
    The use of a resorbable bone tissue support structure of the present invention when a bone defect filling involves surgical procedures that can be performed as a single procedure, or multiple procedures in stages or stages of repair. In one embodiment, a resorbable tissue support structure of the present invention is placed in a bone defect site, and secured to the bone using fixation pins or screws. Alternatively, the resorbable tissue support structure can be externally secured in place with the use of supports. The area is then closed and after a certain period of healing and maturation, the bone will regenerate to repair the defect. EXAMPLES
    The following examples are provided to further illustrate and to facilitate understanding of the description. 20 These specific examples are intended to be illustrative of the description and are not intended to be limiting in any way.
    In a first exemplary embodiment a resorbable support structure is formed from fiber 13-93 by blending 75 grams of fiber 13-93 having an average diameter of approximately 34 µm obtained from a Mo-Sci Corporation, Ro 11a , MO 65401, in bulk, as non-volatile components with 16 grams of HPMC as an organic binder and 20 grams of PMMA with a particle size of 25 to 30 µm 30 as a pore former and approximately 40 grams of deionized water, adjusted as needed to provide a plastically formable mixture. The mixture was extruded into a 14 mm diameter stick and dried in a microwave dryer. The volatile components were burnt in an air purged oven and then heat treated at 720°C for one hour to bond and fuse the 13-93 fiber into the bioresorbable tissue support structure. The porosity for this example was measured to be 69.4%.
    In a second exemplary embodiment a resorbable support structure is formed from the 13-93 fiber by blending 5 grams of 13-93 fiber having an average diameter of approximately 34 µm obtained from Mo-Sci Corporation, Rolla, MO 654 01 , in bulk, and 1 gram of 13-93 bioactive glass in a powder form (also from Mo-Sci Corporation) as non-volatile components with 2 grams of HPMC as an organic binder and 5 grams of PMMA with a particle size of 25-30 µm as a pore former and approximately 8 grams of deionized water, adjusted as needed to provide a plastically formable mixture. The mixture was extruded as a 14 mm diameter stick, and dried in a microwave dryer. The volatile components were burnt in an air purged oven and heat treated at 690°C for 45 minutes to bond and fuse the 13-93 fiber into the bioresorbable tissue support structure using the bioactive glass material to coat the adjacent fiber is overlaid with glass. The porosity for this example was measured to be 76%.
    In a third exemplary embodiment a resorbable support structure is formed from fiber 13-93 by blending 5 grams of fiber 13-93 having an average diameter of approximately 34 µm obtained from Mo-Sci Corporation, Rolla, MO 65401, a bulk, and 2 grams of 13-93 bioactive glass in a powder form (also from Mo-Sci Corporation) as the non-volatile components with 2 grams of HPMC as an organic binder and 5 grams of graphite powder 4015 from
    Asbury Carbons, Asbury, NJ with a particle size distribution of between 150 and 425 µm as a pore former and approximately 10 grams of deionized water, adjusted as needed to provide a plastically formable mixture. The mixture was extruded as a 14 mm diameter stick and dried for 30 minutes at 125°C. The volatile components were burnt in an air purged oven and heat treated at 800°C for 45 minutes to bond and fuse the 13-93 fiber into the bioresorbable tissue support structure using the bioactive glass material to coat the adjacent fiber is overlaid with glass. The porosity for this example was measured to be 66.5% with a compressive strength of 7.0 MPa.
    In a fourth exemplary embodiment a resorbable support structure is formed from fiber 45S5 and fiber 13-93 by blending 45 grams of fiber 13-93 having an average diameter of approximately 34 µm obtained from Mo-Sci Corporation, Rolla, MO 65401, in bulk with 30 grams of 4 5S5 fiber which has an average diameter of 14 µm, 20 (also from Mo-Sci Corporation) as non-volatile components with 16 grams of HPMC as an organic binder and 20 grams of starch which has an average particle size of 50 µm as a pore former and approximately 40 grams of deionized water, adjusted as needed to provide a plastically formable mixture. The mixture was extruded into a 14 mm diameter stick and dried in a microwave dryer. The volatile components were burnt in an air-purged furnace and heat-treated at 715°C for one hour to bond and fuse the 13-93 and 45S5 fiber into the bioresorbable fabric backing structure with fiber-covering glass material. the adjacent and overlapping fiber. The porosity for this example was determined to be 40.4%.
    In a fifth exemplary embodiment a resorbable support structure is formed from fiber 13-93 by blending 5 grams of fiber 13-93 having an average diameter of approximately 34 µm obtained from Mo-Sci Corporation, Rolla, MO 65401, in bulk, and 2 grams of 13-93 bioactive glass in a powder form (also from Mo-Sci Corporation) as non-volatile components with 2 grams of HPMC as an organic binder and 1.5 grams of PMMA as a particle size 100 µm as a pore former and approximately 7 grams of deionized water, adjusted as needed to provide a plastically formable mixture. The mixture was extruded into a 14 mm diameter stick and dried in a microwave dryer. The volatile components were fired in an air purged oven and heated and treated at 680°C for 45 minutes to bond and fuse the 13-93 fiber into the bioresorbable tissue support structure using the bioactive glass material to coat the adjacent fiber and overlaid with glass. The porosity for this example was measured to be 58.5% with a compressive strength of 4.7 MPa.
    In a sixth exemplary embodiment a resorbable support structure is formed from fiber 13-93 by blending 5 grams of fiber 13-93 having an average diameter of approximately 34 µm obtained from Mo-Sci Corporation, Rolla, MO 65401, in bulk as non-volatile components with 2 grams of HPMC as an organic binder and 1.5 grams of PMMA with a particle size of 100 µm as a pore former and approximately 8 grams of deionized water, adjusted as needed to provide a plastically formable mixture. The mixture was extruded into a 14 mm diameter stick and dried in a microwave dryer. The volatile components were burnt in an air purged oven and heat treated at 700°C for 90 minutes to bond and fuse the 13-93 fiber into the bioresorbable tissue support structure using the fiber's bioactive glass material to coat adjacent and overlaid fiber with glass. Porosity by this example was measured to be 47.0% with a compressive strength of 22.5 MPa.
    In a seventh exemplary embodiment a resorbable support structure is formed from fiber 13-93 by blending 5 grams of fiber 13-93 having an average diameter of approximately 34 µm obtained from Mo-Sci Corporation, Rolla, MO 65401, in bulk, and 3 grams of 13-93 bioactive glass in a powder form (also from Mo-Sci Corporation) as the non-volatile components with 2 grams of HPMC as an organic binder and 5 grams of PMMA with a particle size of 15 25 to 30 µm as a pore former and approximately 8 grams of deionized water, adjusted as needed to provide a plastically formable mixture. The mixture was extruded into a 14 mm diameter stick and dried in a microwave dryer. Volatile components 20 were fired in an air purged furnace and heated and treated at 710°C for 45 minutes to bond and fuse fiber 13-93 into the bioresorbable tissue support structure using bioactive glass material to coat the adjacent fiber is overlaid with glass. Porosity by this example was measured to be 50.2% with a compressive strength of 20.1 MPa.
    A method of filling a defect in a bone includes filling a space in the bone with a resorbable tissue support structure comprising bioactive fibers connected in a porous matrix, wherein the porous matrix has a pore size distribution for facilitate bone tissue growth; and the attachment of the resorbable tissue support structure to the bone.
    One method of treating an osteotomy includes filling a space in the bone with a resorbable tissue support structure comprising bioactive fibers bonded in a porous matrix, wherein the porous matrix has a pore size distribution to facilitate the growth of bone tissue; and the attachment of the resorbable tissue support structure to the bone.
    One method of treating a structural failure of a vertebra includes filling a space in the bone with a resorbable tissue support structure comprising bioactive fibers bonded in a porous matrix, wherein the porous matrix has a pore size distribution. to facilitate bone tissue growth; and the attachment of the resorbable tissue support structure to the bone.
    A method of manufacturing a synthetic bone prosthesis includes mixing bioactive fiber with a binder, a pore former and a liquid to provide a plastically formable batch; kneading the formable batch to distribute the bioactive fiber with the pore former and binder, with the formable batch as a homogeneous mass of interwoven and superimposed bioactive fiber; forming the formable batch into a desired shape to provide a molded shape; drying the molded form to remove liquid; heating the molded form 25 to remove the binder and the pore former; and heating the molded form to a bond-forming temperature using a primary heat source and a secondary heat source to form bonds between the superimposed, interwoven bioactive glass fiber.
    In one embodiment, the present invention describes the use of bioactive fibers bonded in a porous matrix, the porous matrix having a pore size distribution to facilitate the growth of bone tissue for the treatment of a bone defect.
    In one embodiment, the present invention describes the use of bioactive fibers bonded in a porous matrix, the porous matrix having a pore size distribution to facilitate the growth of bone tissue for the treatment of an osteotomy.
    In one embodiment, the present invention describes the use of bioactive fibers bonded in a porous matrix, the porous matrix having a pore size distribution to facilitate bone tissue growth for treating a structural failure of multiple parts of a column. spinal.
    The present invention has been described herein in detail with respect to certain illustrative and specific embodiments thereof, and is not to be considered limited thereto, as numerous modifications are possible without departing from the character and scope of the appended claims.
    权利要求:
    Claims (10)
    [0001]
    1. REABSORBABLE THREE-DIMENSIONAL FABRIC SUPPORT STRUCTURE, characterized by comprising: bioactive glass fibers; 5 binding bioactive glass to at least a portion of the bioactive glass fibers; and pore space within the predetermined three-dimensional tissue support structure by the volatile components removed during the binding of bioactive glass to the 10 bioactive glass fibers, wherein the pore space creates a porosity between approximately 40% and approximately 85% in the structure of Resorbable three-dimensional fabric support.
    [0002]
    2. FABRIC SUPPORT STRUCTURE, according to claim 1, characterized in that the bioactive glass fibers and the bioactive glass have a uniform composition.
    [0003]
    3. TISSUE SUPPORT STRUCTURE according to claim 1, characterized in that the pore space within the three-dimensional tissue support structure has a pore size between approximately 100 µm and approximately 500 µm.
    [0004]
    4. FABRIC SUPPORT STRUCTURE, according to claim 4, characterized in that the pore size has a bi-modal size distribution.
    [0005]
    5. FABRIC SUPPORT STRUCTURE, according to claim 1, characterized in that a plurality of bioactive glass fibers is bonded to adjacent bioactive glass fibers, forming bundles of bonded bioactive glass fibers.
    [0006]
    6. FABRIC SUPPORT STRUCTURE, according to claim 1, characterized in that the bioactive glass fibers comprise sodium carbonate, calcium carbonate, phosphorus pentoxide, approximately 45% mol to approximately 60% mol silica, and a molar ratio of approximately 2 to approximately 10 of calcium and phosphate.
    [0007]
    7. FABRIC SUPPORT STRUCTURE, according to claim 1, characterized in that the bioactive glass fibers comprise glass fibers 13-93.
    [0008]
    8. FABRIC SUPPORT STRUCTURE, according to claim 1, characterized in that the bioactive glass fibers have a diameter ranging from approximately 1 μm to approximately 200 μm.
    [0009]
    9. FABRIC SUPPORT STRUCTURE, according to claim 8, characterized in that the bioactive glass fibers have a diameter ranging from approximately 5 μm to approximately 100 μm.
    [0010]
    10. BIOACTIVE TISSUE SUPPORT STRUCTURE, characterized by comprising: a rigid three-dimensional matrix of a bioactive composition formed from a process comprising: the mixture of a bioactive fiber, a binder, a binding agent, a pore former, and a liquid, such as a plastically formable batch; the formation of the plastically formable group as a molded object; drying the molded object to remove the liquid; removal of the binder; .25 removal of the pore former; and heating the molded object to melt and bind the bioactive fiber into the rigid three-dimensional matrix using the binding agent with the pore space defined by the pore former.
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    US20120203355A1|2012-08-09|
    US9968463B2|2018-05-15|
    JP2012532679A|2012-12-20|
    WO2011005933A2|2011-01-13|
    WO2011005935A2|2011-01-13|
    CA2767714A1|2011-01-13|
    CA2767714C|2017-09-26|
    IL217339A|2014-05-28|
    BR112012000327A2|2020-10-27|
    CN102470194B|2014-07-23|
    IL217340D0|2012-02-29|
    IN2012DN01105A|2015-04-10|
    EP2451494A2|2012-05-16|
    US20110106272A1|2011-05-05|
    CA2767715A1|2011-01-13|
    CN102470194A|2012-05-23|
    JP2012532680A|2012-12-20|
    US20150238325A1|2015-08-27|
    US8652368B2|2014-02-18|
    KR20120065322A|2012-06-20|
    BR112012000326A2|2020-10-27|
    CN102470195B|2014-07-23|
    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    EP0051955B1|1980-11-06|1985-04-24|Charles A. Homsy|Porous body-implantable polytetrafluoroethylene composites|
    US4655777A|1983-12-19|1987-04-07|Southern Research Institute|Method of producing biodegradable prosthesis and products therefrom|
    SE455103B|1985-01-09|1988-06-20|Lars Edgar Martin Ehrnford|CARRIER FOR IMMOBILIZATION OF BIOLOGICALLY ACTIVE ORGANIC MATERIAL, WHICH IS MADE BY COMBINED PARTICLES OF A POROS SINTRAD GLASS FIBER MATERIAL|
    US4604097B1|1985-02-19|1991-09-10|Univ Dayton|
    US5149857A|1989-06-07|1992-09-22|Mitsubishi Gas Chemical Company, Inc.|Process for production of sulfonium compounds|
    US5009822A|1989-07-17|1991-04-23|University Of Florida|Alumina-or alumina/zirconia-silicon carbide whisker ceramic composites and methods of manufacture|
    US5236458A|1989-09-06|1993-08-17|S.A. Fbfc International|Bioreactive material for a prosthesis or composite implants|
    DK0532582T3|1990-06-01|1996-01-29|Du Pont|Composite orthopedic implant with varying modulus of elasticity|
    EP0672117A4|1992-08-13|1996-06-12|Univ Pennsylvania|BIOACTIVE MATERIAL TEMPLATE FOR -i SYNTHESIS OF BONE TISSUE.|
    CN1087279A|1992-11-27|1994-06-01|中国科学院光电技术研究所|Bio-active devitroceram artificial and method for making thereof|
    US5419857A|1993-08-17|1995-05-30|Praxair Technology, Inc.|Thermal removal of binders from ceramic-particle bodies|
    US5468544A|1993-11-15|1995-11-21|The Trustees Of The University Of Pennsylvania|Composite materials using bone bioactive glass and ceramic fibers|
    US5721049A|1993-11-15|1998-02-24|Trustees Of The University Of Pennsylvania|Composite materials using bone bioactive glass and ceramic fibers|
    US5629186A|1994-04-28|1997-05-13|Lockheed Martin Corporation|Porous matrix and method of its production|
    FI101129B|1995-01-13|1998-04-30|Vivoxid Oy|New bioactive glasses and their use|
    US6162537A|1996-11-12|2000-12-19|Solutia Inc.|Implantable fibers and medical articles|
    AU8681098A|1997-08-01|1999-03-08|Massachusetts Institute Of Technology|Three-dimensional polymer matrices|
    US6296667B1|1997-10-01|2001-10-02|Phillips-Origen Ceramic Technology, Llc|Bone substitutes|
    EP1027304B1|1997-10-03|2005-07-13|Corning Incorporated|Method for firing ceramic honeycomb bodies|
    ID25445A|1997-12-02|2000-10-05|Corning Inc|TOWEL TOWELS FOR BURNING CERAMIC BEES, CERAMIC|
    US6325963B1|1997-12-22|2001-12-04|Corning Incorporated|Method for firing ceramic honeycomb bodies|
    DE69838183T3|1997-12-22|2014-12-11|Corning Incorporated|Tunnel kiln for firing ceramic honeycomb structural bodies|
    US6187329B1|1997-12-23|2001-02-13|Board Of Regents Of The University Of Texas System|Variable permeability bone implants, methods for their preparation and use|
    US6406498B1|1998-09-04|2002-06-18|Bionx Implants Oy|Bioactive, bioabsorbable surgical composite material|
    US6146892A|1998-09-28|2000-11-14|The Regents Of The University Of Michigan|Fibrillar matrices|
    US6110484A|1998-11-24|2000-08-29|Cohesion Technologies, Inc.|Collagen-polymer matrices with differential biodegradability|
    FI110063B|1998-12-11|2002-11-29|Antti Yli-Urpo|New bioactive product and its use|
    US6200347B1|1999-01-05|2001-03-13|Lifenet|Composite bone graft, method of making and using same|
    WO2000055802A1|1999-03-17|2000-09-21|Siemens Aktiengesellschaft|Interaction device|
    US6187239B1|1999-03-30|2001-02-13|Tokyo Seihinkaihatsu Kenkyusho|Manufacture method of article similar to unglazed ceramic plate|
    EP1173235B1|1999-04-16|2004-05-12|Rutgers, The State University|Porous polymer scaffolds for tissue engineering|
    CA2389627A1|1999-11-01|2001-05-10|Osteobiologics, Inc.|Biodegradable polymer/ceramic implant material with bimodal degradation profile|
    US6451059B1|1999-11-12|2002-09-17|Ethicon, Inc.|Viscous suspension spinning process for producing resorbable ceramic fibers and scaffolds|
    US20040009228A1|1999-11-30|2004-01-15|Pertti Tormala|Bioabsorbable drug delivery system for local treatment and prevention of infections|
    FI20000515A0|2000-03-07|2000-03-07|Heimo Ylaenen|Procedure for making a surface of bioactive glass hardened|
    EP1272439A2|2000-03-24|2003-01-08|Lyles, Mark B.|Diagnostic devices containing porous material|
    US20040009598A1|2001-07-11|2004-01-15|Hench Larry L|Use of bioactive glass compositions to stimulate osteoblast production|
    FI20001696A|2000-07-21|2002-01-22|Jvs Polymers Oy|Biologically active material|
    US20020082697A1|2000-12-22|2002-06-27|Damien Christopher J.|Implantable osteogenic material|
    US7005135B2|2001-01-30|2006-02-28|Ethicon Inc.|Glass scaffolds with controlled resorption rates and methods for making same|
    FI117963B|2001-04-26|2007-05-15|Eija Marjut Pirhonen|Material that replaces bone|
    WO2002087647A1|2001-04-26|2002-11-07|Eija Pirhonen|Bone grafting materials|
    US6626950B2|2001-06-28|2003-09-30|Ethicon, Inc.|Composite scaffold with post anchor for the repair and regeneration of tissue|
    US20030147860A1|2002-02-07|2003-08-07|Marchosky J. Alexander|Compositions and methods for forming and strengthening bone|
    US20030220692A1|2002-02-09|2003-11-27|Shapiro Irving M.|Preparations of nucleus pulposus cells and methods for their generation, identification, and use|
    US6955716B2|2002-03-01|2005-10-18|American Dental Association Foundation|Self-hardening calcium phosphate materials with high resistance to fracture, controlled strength histories and tailored macropore formation rates|
    US8313742B2|2002-03-29|2012-11-20|Depuy Acromed, Inc.|Cell-containing bone graft material|
    US7166133B2|2002-06-13|2007-01-23|Kensey Nash Corporation|Devices and methods for treating defects in the tissue of a living being|
    WO2004032988A2|2002-10-08|2004-04-22|Osteotech, Inc.|Coupling agents for orthopedic biomaterials|
    US20050118236A1|2002-12-03|2005-06-02|Gentis Inc.|Bioactive, resorbable scaffolds for tissue engineering|
    US20070190108A1|2004-05-17|2007-08-16|Arindam Datta|High performance reticulated elastomeric matrix preparation, properties, reinforcement, and use in surgical devices, tissue augmentation and/or tissue repair|
    US7217293B2|2003-11-21|2007-05-15|Warsaw Orthopedic, Inc.|Expandable spinal implant|
    ITPD20030286A1|2003-11-27|2005-05-28|Fidia Advanced Biopolymers Srl|COMPOSITE MULTISTRATE STRUCTURES CONTAINING HYALURONIC ACID|
    US7625581B2|2003-12-19|2009-12-01|Ethicon, Inc.|Tissue scaffolds for use in muscoloskeletal repairs|
    US8597331B2|2004-12-10|2013-12-03|Life Spine, Inc.|Prosthetic spinous process and method|
    US20060216321A1|2005-03-24|2006-09-28|Sdgi Holdings, Inc.|Solvent based processing technologies for making tissue/polymer composites|
    FI20055194A|2005-04-27|2006-10-28|Bioretec Oy|Bioabsorbent and bioactive composite material and process for manufacturing composite|
    WO2006118554A1|2005-05-02|2006-11-09|Shanghai Institute Of Ceramics|A degradable, macroporous bioactive glass scaffold as well as its preparation and manufacturing methods|
    US20070055373A1|2005-09-08|2007-03-08|Zimmer Spine, Inc.|Facet replacement/spacing and flexible spinal stabilization|
    US20070087059A1|2005-10-17|2007-04-19|Frank Everaerts|Bioactive delivery matrix compositions and methods|
    US20070123984A1|2005-10-26|2007-05-31|Zimmer Technology, Inc.|Ligament attachment and repair device|
    US20070098799A1|2005-10-28|2007-05-03|Zimmer, Inc.|Mineralized Hydrogels and Methods of Making and Using Hydrogels|
    KR20090057392A|2006-08-18|2009-06-05|지이오2 테크놀로지스 인코포레이티드|An extruded porous substrate having inorganic bonds|
    US20070152364A1|2005-11-16|2007-07-05|Bilal Zuberi|Process for extruding a porous substrate|
    US7758803B2|2006-01-11|2010-07-20|Jiang Chang|Resorbable macroporous bioactive glass scaffold and method of manufacture|
    US20090299476A1|2006-05-19|2009-12-03|Ashish Diwan|Tissue prosthesis|
    GB0612028D0|2006-06-16|2006-07-26|Imp Innovations Ltd|Bioactive glass|
    DE602006011323D1|2006-09-20|2010-02-04|Inion Oy|Bioactive glass compositions|
    US7923020B2|2006-09-29|2011-04-12|Depuy Products, Inc.|Composite for implantation in the body of an animal and method for making the same|
    US7718616B2|2006-12-21|2010-05-18|Zimmer Orthobiologics, Inc.|Bone growth particles and osteoinductive composition thereof|
    US7567817B2|2007-05-14|2009-07-28|Geo2 Technologies, Inc.|Method and apparatus for an extruded ceramic biosoluble fiber substrate|
    US7855163B2|2007-05-14|2010-12-21|Geo2 Technologies, Inc.|Low coefficient of thermal expansion bonding system for a high porosity ceramic body and methods of manufacture|
    US7781372B2|2007-07-31|2010-08-24|GE02 Technologies, Inc.|Fiber-based ceramic substrate and method of fabricating the same|
    US8641774B2|2007-09-14|2014-02-04|The Curators Of The University Of Missouri|Synthetic osteochondral composite and method of fabrication thereof|
    US20110142902A1|2008-05-27|2011-06-16|Imperial Innovations Limited|Hypoxia Inducing Factor Stabilising Glasses|
    US9456890B2|2009-01-15|2016-10-04|The Curators Of The University Of Missouri|Scaffold for bone and tissue repair in mammals|
    US8353966B2|2009-01-15|2013-01-15|The Curators Of The University Of Missouri|Scaffold for bone and tissue repair in mammals|
    EP2243749B1|2009-04-23|2015-04-08|PURAC Biochem BV|Resorbable and biocompatible fibre glass compositions and their uses|
    US20110206828A1|2009-07-10|2011-08-25|Bio2 Technologies, Inc.|Devices and Methods for Tissue Engineering|
    US9775721B2|2009-07-10|2017-10-03|Bio2 Technologies, Inc.|Resorbable interbody device|
    CA2767714C|2009-07-10|2017-09-26|Bio2 Technologies, Inc.|Resorbable three-dimensional tissue scaffold fabricated from bioactive glass fibers bonded by bioactive glass|
    US8481066B2|2009-07-16|2013-07-09|The Curators Of The University Of Missouri|Scaffold for tissue regeneration in mammals|
    US8287896B2|2010-01-06|2012-10-16|The Curators Of The University Of Missouri|Scaffolds with trace element for tissue regeneration in mammals|
    AU2013217649B2|2012-02-10|2016-10-06|Synthes Gmbh|Porous implant materials and related methods|
    US9066998B2|2012-03-02|2015-06-30|Bio2 Technologies, Inc.|Devices and method for tissue engineering|
    US20140050765A1|2012-08-14|2014-02-20|Bio2 Technologies, Inc.|Devices and Methods for Tissue Engineering|
    US20140212469A1|2013-01-28|2014-07-31|Missouri University Of Science And Technology|Surface functional bioactive glass scaffold for bone regeneration|
    US10238772B2|2013-03-15|2019-03-26|The Curators Of The University Of Missouri|Biodegradable composite scaffold for repairing defects in load-bearing bones|US6024162A|1994-12-28|2000-02-15|Nippon Steel Corporation|Continuous casting method for billet|
    US10524916B2|2006-01-11|2020-01-07|Novabone Products, Llc|Resorbable macroporous bioactive glass scaffold and method of manufacture|
    US8349015B2|2009-02-11|2013-01-08|Howmedica Osteonics Corp.|Intervertebral implant with integrated fixation|
    US20110206828A1|2009-07-10|2011-08-25|Bio2 Technologies, Inc.|Devices and Methods for Tissue Engineering|
    CA2767714C|2009-07-10|2017-09-26|Bio2 Technologies, Inc.|Resorbable three-dimensional tissue scaffold fabricated from bioactive glass fibers bonded by bioactive glass|
    US9775721B2|2009-07-10|2017-10-03|Bio2 Technologies, Inc.|Resorbable interbody device|
    US8567162B2|2009-10-29|2013-10-29|Prosidyan, Inc.|Dynamic bioactive bone graft material and methods for handling|
    BR112012028020B1|2010-05-06|2018-11-27|Bio2 Technologies, Inc|method to manufacture a synthetic bone prosthesis|
    US9066998B2|2012-03-02|2015-06-30|Bio2 Technologies, Inc.|Devices and method for tissue engineering|
    KR101941244B1|2012-03-26|2019-01-22|모사이 코퍼레이션.|Bioactive glass scaffolds, and method of making|
    US8449904B1|2012-03-26|2013-05-28|Mosci, Corp.|Bioactive glass scaffolds, and method of making|
    US11225430B2|2012-03-26|2022-01-18|Steven Jung|Bioactive glass scaffolds, and method of making|
    CN102826752B|2012-08-23|2015-07-15|北京大清生物技术有限公司|Bioactive mineral powder containing quasi-nanometer particles, preparation method and application thereof in dental treatment|
    US9376540B2|2013-01-25|2016-06-28|Eastman Kodak Company|Particles with designed different sized discrete pores|
    US9381274B2|2013-03-14|2016-07-05|Prosidyan, Inc.|Bone graft implants containing allograft|
    US8889178B2|2013-03-14|2014-11-18|Prosidyan, Inc|Bioactive porous bone graft compositions in synthetic containment|
    US8883195B2|2013-03-14|2014-11-11|Prosidyan, Inc.|Bioactive porous bone graft implants|
    US9045362B2|2013-03-15|2015-06-02|Mosci Corp.|Bioactive glass scaffolds, and method of making|
    CN103191463B|2013-04-03|2014-10-29|上海师范大学|Preparation method of three-dimensional ordered porous bracket material of chitosan fiber/bioactive glass|
    AU2013221955B2|2013-04-12|2017-06-22|Mosci Corp.|Bioactive glass scaffolds, and method of making|
    AU2016200179B2|2015-01-14|2020-09-17|Stryker European Operations Holdings Llc|Spinal implant with porous and solid surfaces|
    US10603182B2|2015-01-14|2020-03-31|Stryker European Holdings I, Llc|Spinal implant with fluid delivery capabilities|
    CA2930123A1|2015-05-18|2016-11-18|Stryker European Holdings I, Llc|Partially resorbable implants and methods|
    US20170056190A1|2015-08-27|2017-03-02|Wright Medical Technology, Inc.|Subtalar biofoam wedge|
    US10485897B2|2015-10-12|2019-11-26|Erik Erbe|Osteogenic and angiogenic implant material|
    US11013836B2|2016-06-16|2021-05-25|The Curators Of The University Of Missouri|Inorganic biodegradable substrates for devices and systems|
    EP3459502A1|2017-09-20|2019-03-27|Stryker European Holdings I, LLC|Spinal implants|
    CN109966549B|2017-12-28|2021-12-31|北京纳通科技集团有限公司|Three-dimensional bionic bone repair material and preparation method thereof|
    WO2020008558A1|2018-07-04|2020-01-09|オリンパス株式会社|Bone substitute and method for producing bone substitute|
    US20210236693A1|2020-01-30|2021-08-05|SDIP Innovations Pty Ltd|Bioresorbable implant with inside-out resorption for enhanced bone ingrowth and tissue integration and method of manufacturing thereof|
    US20210260242A1|2020-02-24|2021-08-26|Prosidyan, Inc.|Bioactive implantable devices, and composite biomaterials and methods for making the same|
    WO2022011173A1|2020-07-08|2022-01-13|4Web, Inc.|Implants having bone growth promoting agents contained within biodegradable materials|
    WO2022031709A1|2020-08-03|2022-02-10|Biorez, Inc.|Composite scaffold for the repair, reconstruction, and regeneration of soft tissues|
    法律状态:
    2020-11-03| B06U| Preliminary requirement: requests with searches performed by other patent offices: procedure suspended [chapter 6.21 patent gazette]|
    2020-12-08| B06F| Objections, documents and/or translations needed after an examination request according [chapter 6.6 patent gazette]|
    2021-02-09| B09A| Decision: intention to grant [chapter 9.1 patent gazette]|
    2021-04-20| B16A| Patent or certificate of addition of invention granted|Free format text: PRAZO DE VALIDADE: 20 (VINTE) ANOS CONTADOS A PARTIR DE 08/07/2010, OBSERVADAS AS CONDICOES LEGAIS. PATENTE CONCEDIDA CONFORME MEDIDA CAUTELAR DE 07/04/2021 - ADI 5.529/DF |
    优先权:
    申请号 | 申请日 | 专利标题
    US22467509P| true| 2009-07-10|2009-07-10|
    US61/224,675|2009-07-10|
    US23476809P| true| 2009-08-18|2009-08-18|
    US61/234,768|2009-08-18|
    PCT/US2010/041331|WO2011005933A2|2009-07-10|2010-07-08|Devices and methods for tissue engineering|
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